Relationship between the angiotensin-converting enzyme genotype and the forearm vasodilator response to estrogen replacement therapy in postmenopausal women

OBJECTIVES We sought to evaluate the relationship between the angiotensin-c onverting enzyme (ACE) genotype and the change in forearm vasoreactivity in response to a three-month course of oral estrogen in postmenopausal women. BACKGROUND The ACE genotype is a known predictor of the response to an ACE inhibitor drug; however, it is not clear whether it can modify the effect o f estrogen replacement therapy (ERT) on endothelial function in postmenopau sal women. METHODS Fifty-five postmenopausal women received 0.625 mg of conjugated equ ine estrogen daily for three months. Forearm blood flow (FBF) was measured by strain-gauge plethysmography. RESULTS Twenty-one, 25 and 9 patients had the insertion/deletion (ID), II a nd DD genotypes, respectively. Plasma ACE activity was significantly higher at baseline in patients with either the DD or ID genotype than in those wi th the II genotype (p < 0.05). A significant decrease in plasma ACE activit y with ERT was seen in the ID and II genotypes (p < 0.05), but not in the E D genotype. There were no significant differences in the FBF responses to r eactive hyperemia at baseline between the three groups. Estrogen replacemen t therapy did not alter the FBF response to reactive hyperemia in the DD ge notype (4.0 +/- 1.3%), although ERT significantly increased the FBF respons e in the IB and II genotypes (32.6 +/- 7.5% and 30.6 +/- 6.5%, respectively ; p < 0.05). Forearm blood flow after administration of sublingual nitrogly cerin did not change over three months in any of the three groups. CONCLUSIONS These findings suggest that the effect of ERT in postmenopausal women on forearm endothelial function may be determined in part by the gen otype of the ACE gene. (J Am Coll Cardiol 2001;37:1529-35) (C) 2001 by the American College of Cardiology.